The purpose of this proposal is to try establish a relationship between concentrations of one of two compounds, known to have effects on the male reproductive system, and their metabolites in the seminal compartments (seminal plasma and germ cell) with indices of spermatotoxicity (sperm count, motility, viability, morphometry, and morphology). Additionally, it will be determined if threshold concentrations of the xenobiotic can be identfied for the affected spermatogenic parameters, how recovery is related to different dosages, and how these two compounds, representing two different chemical classes, differ in their distribution, effects, and ability to predict risk from their seminal concentrations. The compounds chosen for study are 1,2-dibromo-3-chloropropane and 2-ethoxyethanol. All experiments will be performed on adult, male rabbits. There will be three phases to this study along with the development of the analytical techniques. The analytical techniques will include use of GC, HPLC, and capillary GC-mass spectroscopy. The first phase will determine a rough time course for each compound in the semen using radiolabelled compounds. The second phase will be used to identify the actual metabolites in the seminal compartments, and to more accurately determine the kinetics in the semen. The last phase is the study proper and will consist of subchronic exposure to one of the compounds with repeated semen sampling of the males. The semen will be analyzed for parent and metabolites and spermatogenic parameters will be assessed. This project is important as concern for male reproductive toxicity is growing. Moreover, this approach is noninvasive and may be applicable in the human population.